International Immunology Advance Access originally published online on October 7, 2005
International Immunology 2005 17(11):1505-1512; doi:10.1093/intimm/dxh328
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Characterization of human phagocyte-derived chitotriosidase, a component of innate immunity
1 Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE, Amsterdam, The Netherlands
2 Genzyme Corporation, Framingham, MA 01701, Du Pont, USA
3 Section of Infectious Diseases, Evan Memorial Department of clinical Research, Boston Medical Center, Boston, MA 02118, USA
4 Sanquin Research at CLB, Amsterdam, The Netherlands
5 Present address: Department of Virology, Institute of Medical Technology and Tampere University Hospital, Tampere FN-33014, Finland
Correspondence to: J. M. F. G. Aerts; E-mail: j.m.aerts{at}amc.uva.nl
Man has been found to produce highly conserved chitinases. The most prominent is the phagocyte-derived chitotriosidase, the plasma levels of which are markedly elevated in some pathological conditions. Here, we report that both polymorphonuclear neutrophils (PMNs) and macrophages (m
) are a source of chitotriosidase. The enzyme is located in specific granules of human PMNs and secreted following stimulation with granulocyte macrophage colony-stimulating factor (GM-CSF). In addition, GM-CSF induces expression of chitotriosidase in m
that constitutively secrete the enzyme and partly accumulate it in their lysosomes. Studies with recombinant human chitotriosidase revealed that the enzyme targets chitin-containing fungi. These findings are consistent with earlier observations concerning anti-fungal activity of homologous plant chitinases and beneficial effects of GM-CSF administration in individuals suffering from invasive fungal infections. In conclusion, chitotriosidase should be viewed as a component of the innate immunity that may play a role in defence against chitin-containing pathogens and the expression and release of which by human phagocytes is highly regulated.
Keywords: human, monocyte/macrophage, neutrophil
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